Sex hormone and gender difference - Role of testosterone on male predominance in Brugada syndrome

Introduction: The clinical phenotype is 8 to 10 times more prevalent in males than in females in patients with Brugada syndrome. Brugada syndrome has been reported to be thinner than asymptomatic normal controls. We tested the hypothesis that higher testosterone level associated with lower visceral fat may relate to Brugada phenotype and male predominance. Methods and Results: We measured body-mass index (BMI), body fat percentage (BF%), and several hormonal levels, including testosterone, in 48 Brugada males and compared with those in 96 age-matched control males. Brugada males had significantly higher testosterone (631 +/- 176 vs 537 +/- 158 ng/dL; P = 0.002), serum sodium, potassium, and chloride levels than those in control males by univariate analysis, and even after adjusting for age, exercise, stress, smoking, and medication of hypertension, diabetes, and hyperlipidemia, whereas there were no significant differences in other sex and thyroid hormonal levels. Brugada males had significantly lower BMI (22.1 +/- 2.9 vs 24.6 +/- 2.6 kg/m(2); P < 0.001) and BF% (19.6 +/- 4.9 vs 23.1 +/- 4.7%; P < 0.001) than control males. Testosterone level was inversely correlated with BMI and BF% in both groups, even after adjusting for the confounding variables. Conditional logistic regression models analysis showed significant positive and inverse association between Brugada syndrome and hypertestosteronemia (OR:3.11, 95%CI:1.22-7.93, P = 0.017) and BMI (OR:0.72, 95%CI:0.61-0.85, P < 0.001), respectively. Conclusions: Higher testosterone level associated with lower visceral fat may have a significant role in the Brugada phenotype and male predominance in Brugada syndrome.